1a: Epidemiological studies support inverse associations between coffee intake and cardiometabolic traits, but provide no insight to causality or mechanisms. The latter may be addressed by Mendelian randomization and gene-coffee interaction studies. To investigate the causal and mechanistic role of coffee in cardiometabolic health we aim to

3) Study the causal and mechanistic role of coffee consumption for development of T2D and CVD

1b: Coffee is one of the most widely consumed beverages in the world and thus represents a significant opportunity to positively affect cardiometabolic health globally. In efforts to establish causality and potential mechanisms we are proposing health-related research that is in public interest and thus we believe our study meets the UK Biobank’s purpose.

1c: We will first explore the observational associations of coffee consumption with incident T2D, CHD, ischemic and hemorrhagic stroke, HF and risk factors for T2D and CVD (Aim 1). We will then identify genetic variants associated with coffee consumption and develop robust GS for use in any genetic epidemiological analysis of coffee and health (Aim 2). Finally, we apply these GS in studies of the causal and mechanistic role of coffee consumption for development of T2D and CVD using Mendelian randomization (MR) and gene-coffee interaction frameworks (Aim 3).